Histologic inflammation and collagen content are not positively correlated in human BPH
Andrew J. Schneider,
Emily C. Serrell,
Matthew Grimes
et al.
Abstract:IntroductionRecent clinical studies have implicated prostate inflammation and fibrosis in the development of bladder outlet obstruction and lower urinary tract symptoms (LUTS). Studies utilizing rodent models, including work in our laboratory, have shown prostate fibrosis to occur as a consequence of inflammation. However, the relationship between collagen content and inflammation in human tissue samples obtained from surgical treatment of benign prostatic hypererplasia (BPH)/LUTS has not to our knowledge been… Show more
BackgroundBenign prostatic hyperplasia (BPH) is a condition generally associated with advanced age in men that can be accompanied by bothersome lower urinary tract symptoms (LUTS) including intermittency, weak stream, straining, urgency, frequency, and incomplete bladder voiding. Pharmacotherapies for LUTS/BPH include alpha‐blockers, which relax prostatic and urethral smooth muscle and 5ɑ‐reductase inhibitors such as finasteride, which can block conversion of testosterone to dihydrotestosterone thereby reducing prostate volume. Celecoxib is a cyclooxygenase‐2 inhibitor that reduces inflammation and has shown some promise in reducing prostatic inflammation and alleviating LUTS for some men with histological BPH. However, finasteride and celecoxib can reduce mitochondrial function in some contexts, potentially impacting their efficacy for alleviating BPH‐associated LUTS.MethodsTo determine the impact of these pharmacotherapies on mitochondrial function in prostate tissues, we performed immunostaining of mitochondrial Complex I (CI) protein NADH dehydrogenase [ubiquinone] iron‐sulfur protein 3 (NDUFS3) and inflammatory cells on BPH specimens from patients naïve to treatment, or who were treated with celecoxib and/or finasteride for 28 days, as well as prostate tissues from male mice treated with celecoxib or vehicle control for 28 days. Quantification and statistical correlation analyses of immunostaining were performed.ResultsNDUFS3 immunostaining was decreased in BPH compared to normal adjacent prostate. Patients treated with celecoxib and/or finasteride had significantly decreased NDUFS3 in both BPH and normal tissues, and no change in inflammatory cell infiltration compared to untreated patients. Mice treated with celecoxib also displayed a significant decrease in NDUFS3 immunostaining and no change in inflammatory cell infiltration.ConclusionsThese findings suggest that celecoxib and/or finasteride are associated with an overall decrease in NDUFS3 levels in prostate tissues but do not impact the presence of inflammatory cells, suggesting a decline in mitochondrial CI function in the absence of enhanced inflammation. Given that BPH has recently been associated with increased prostatic mitochondrial dysfunction, celecoxib and/or finasteride may exacerbate existing mitochondrial dysfunction in some BPH patients thereby potentially limiting their overall efficacy in providing metabolic stability and symptom relief.
BackgroundBenign prostatic hyperplasia (BPH) is a condition generally associated with advanced age in men that can be accompanied by bothersome lower urinary tract symptoms (LUTS) including intermittency, weak stream, straining, urgency, frequency, and incomplete bladder voiding. Pharmacotherapies for LUTS/BPH include alpha‐blockers, which relax prostatic and urethral smooth muscle and 5ɑ‐reductase inhibitors such as finasteride, which can block conversion of testosterone to dihydrotestosterone thereby reducing prostate volume. Celecoxib is a cyclooxygenase‐2 inhibitor that reduces inflammation and has shown some promise in reducing prostatic inflammation and alleviating LUTS for some men with histological BPH. However, finasteride and celecoxib can reduce mitochondrial function in some contexts, potentially impacting their efficacy for alleviating BPH‐associated LUTS.MethodsTo determine the impact of these pharmacotherapies on mitochondrial function in prostate tissues, we performed immunostaining of mitochondrial Complex I (CI) protein NADH dehydrogenase [ubiquinone] iron‐sulfur protein 3 (NDUFS3) and inflammatory cells on BPH specimens from patients naïve to treatment, or who were treated with celecoxib and/or finasteride for 28 days, as well as prostate tissues from male mice treated with celecoxib or vehicle control for 28 days. Quantification and statistical correlation analyses of immunostaining were performed.ResultsNDUFS3 immunostaining was decreased in BPH compared to normal adjacent prostate. Patients treated with celecoxib and/or finasteride had significantly decreased NDUFS3 in both BPH and normal tissues, and no change in inflammatory cell infiltration compared to untreated patients. Mice treated with celecoxib also displayed a significant decrease in NDUFS3 immunostaining and no change in inflammatory cell infiltration.ConclusionsThese findings suggest that celecoxib and/or finasteride are associated with an overall decrease in NDUFS3 levels in prostate tissues but do not impact the presence of inflammatory cells, suggesting a decline in mitochondrial CI function in the absence of enhanced inflammation. Given that BPH has recently been associated with increased prostatic mitochondrial dysfunction, celecoxib and/or finasteride may exacerbate existing mitochondrial dysfunction in some BPH patients thereby potentially limiting their overall efficacy in providing metabolic stability and symptom relief.
Benign prostatic hyperplasia (BPH) is one of the most common benign diseases in middle-aged and elderly men. Its main clinical manifestations are frequent urination, urgent urination, weak urine flow, other lower urinary tract symptoms, serious urinary retention, and urinary incontinence. Chinese herbal compounds are widely used in the clinical treatment of BPH with good efficacy and safety, reflecting the advantages of multi-target and multi-approach traditional Chinese medicine (TCM) treatment. There is usually a high level of inflammation in the affected area of BPH, and its persistence affects the whole body, causing multiple complications and accelerating the development of the disease. Inflammation can directly stimulate the proliferation of prostate cells and drive other pathological mechanisms to jointly promote the development of diseases, such as participating in oxidative stress, driving growth factor synthesis, destroying the imbalance between apoptosis and proliferation, and promoting fibrosis. To more fully elucidate the mechanism of action of Chinese herbal compounds in the treatment of BPH, this paper reviews the literature in recent years, beginning with basic research on the intervention of Chinese herbal compounds in BPH inflammation, to provide further ideas for relevant research on the prevention and treatment of BPH inflammation by TCM.
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